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Thromb Haemost 1999; 82(04): 1302-1306
DOI: 10.1055/s-0037-1614380
Review Article
Schattauer GmbH

Pretreatment with Soluble Thrombomodulin Prevents Intrasinusoidal Coagulation and Liver Dysfunction following Extensive Hepatectomy in Cirrhotic Rats

Toshimi Kaido
1   From the Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto,
,
Akira Yoshikawa
1   From the Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto,
,
Shin-ichi Seto
1   From the Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto,
,
Shoji Yamaoka
1   From the Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto,
,
Hiroaki Furuyama
1   From the Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto,
,
Shigeki Arii
1   From the Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto,
,
Yasuo Takahashi
2   Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd., Shizuoka, Japan
,
Masayuki Imamura
1   From the Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto,
› Author Affiliations
Further Information

Publication History

Received 31 December 1998

Accepted after revision 25 May 1999

Publication Date:
08 December 2017 (online)

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Summary

The major cause of posthepatectomy liver dysfunction is supposed to be microcirculatory disturbance caused by imbalance of intrasinusoidal coagulation equilibrium. Thrombomodulin (TM) is a potent anticoagulant expressed on the endothelial cell surface that regulates the coagulation system by binding thrombin and accelerating the thrombin-catalyzed activation of protein C. Therefore, we examined the effect of soluble TM purified from human urine (UTM) on intrasinusoidal coagulation in cirrhotic rats. Dimethylnitrosamine-induced cirrhotic rats underwent 70% hepatectomy and received endotoxin 48 h after. UTM or vehicle alone was intravenously administered to each rat 30 min before endotoxin injection. UTM treatment attenuated the increases in cytosolic enzymes and serum hyaluronic acid level. The UTM supply improved the survival rate of the rats at 12 h after endotoxin challenge. Histologically, intrasinusoidal fibrin depositions and massive hepatocellular necrosis observed in control rats were scarcely found in UTM-treated rats. Immunohistochemical examination revealed that marked TM stains in sinusoidal endothelial cells were well preserved in UTM-treated rats. In conclusion, UTM administration prevented intrasinusoidal fibrin depositions and attenuated posthepatectomy liver dysfunction in cirrhotic rats.

 

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